THE EFFECT OF NECA, CGS 21680, PSB 603 ON FATTY ACID TRANSPORT AND OXIDATION IN SKELETAL MUSCLE CELLS

Adenosine is a strong modulator of gene expression, which underpins some of its potential expected effects in skeletal muscle in terms of fatty acid metabolism.  Accumulating evidence highlights a critical role for the adenosine system in the regulation of fatty acid metabolism and obesity. However, its molecular signaling role in fatty acid transport and oxidation in skeletal muscle is less clear. The aim of the present study was to examine whether acute and chronic treatment of skeletal muscle cells in vitro with stable adenosine analogue NECA, selective adenosine A2B receptors antagonist/inverse agonist PSB 603, and/or selective adenosine A2A receptors agonist CGS 21680 affects mRNA expression of key metabolic genes in skeletal muscle. Rat L6 skeletal muscle cells were treated with NECA, PSB 603 and CGS 21680 for determination the mRNA expression of genes involved in fatty acid transport and oxidation (CPT1B, ACCβ and LCAD) using QRT-PCR (Probe-based). The results of the present study have shown for the first time that NECA alters the expression of a number of genes (CPT1B, ACCβ and LCAD). Moreover, this is the first study demonstrating that PSB 603 alters the expression of a number of genes (CPT1B, and ACCβ). To our knowledge, this is the first study demonstrating an alteration of CPT1B, and LCAD genes by CGS 21680. Adenosine A2B receptors mediate both NECA-induced LCAD, NECA-inhibited ACCβ, and NECA-modulated CPT1B mRNA gene expression in skeletal muscle cells. Collectively, these data reveal adenosine A2B receptors as a novel target to consider in our understanding of metabolic function in skeletal muscle and risk for the development of metabolic-based diseases.